Various kinds of detectors and signal recording technologies are employed in many different kinds of instruments for the detection and measurement of particles such as photons, electrons, ions, and neutral particles. For the purposes of the present invention disclosure, the present invention will be described with respect to the specific application as a detection system for ions in a Time-of-Flight mass spectrometer; however, it should be appreciated that the present invention is applicable and provides enhanced performance for the measurement of other types of particles in other types of apparatus, such as the detection and recording of photons in optical spectrometers.
Mass spectrometers are used to analyze solid, liquid or gaseous sample substances containing elements or compounds or mixtures of elements or compounds by measuring the mass-to-charge (m/z) values of ions produced from a sample substance in an ion source. Generally, ions are extracted from the ion source and transported into the mass spectrometer, where they are differentiated according their m/z values. The relative intensities of the differentiated m/z ions are measured with a detector and associated signal processing electronics. In a typical Time-of-Flight (ToF) mass spectrometer, ions are differentiated according to their m/z values by pulse-accelerating the population of ions in a source region to a nominally identical kinetic energy as they enter a field free flight tube. Ions of different m/z values but with a common nominal kinetic energy will have velocities that vary inversely with the square root of the m/z value. Therefore, the ion population separates spatially during their flight, and they will arrive at a detector located a fixed distance away with a time dependence that varies directly with the square root of their m/z value. The function of the ToF detector is to produce an amplified output signal that accurately reflects the relative intensities and time dependence of ions with a spectrum of m/z values as they impinge on the detector surface. The fidelity with which the detector and associated signal processing electronics are able to perform this function has a strong impact on the performance of the ToF mass spectrometer with respect to m/z resolving power, signal dynamic range, signal-to-noise, and abundance sensitivity.
A detector must satisfy a number of basic requirements in order to be viable as a detector in a ToF mass spectrometer (although such requirements may be different for other types of instrumentation, such as optical spectrometers). One of these requirements is that the detector must present a planar surface to the impinging ions. Because ions arriving at the detector of a ToF mass spectrometer are typically dispersed over some distance orthogonal to the ToF analyzer axis direction, a non-planar detector surface will produce a variation in flight distances, and therefore flight times, for ions of any particular m/z value, resulting in a degradation of the m/z resolving power. Another requirement is that the frequency response bandwidth of the detector, as well as that of the associated signal recording electronics, must be great enough to produce an output signal waveform that accurately reflects the time dependence and/or intensity of the arriving ion flux. Generally, bandwidths in the hundreds of megahertz to gigahertz range and above are required in current practice.
Still another requirement is that the detector must typically provide amplification, or ‘gain’, of the arriving ion current sufficient to produce a measurable output signal that corresponds to the arrival of a single ion. Often, the detector must also be capable of producing an output amplitude that is linearly proportional to many simultaneously arriving ions of any particular m/z value. Therefore, a fast analog waveform recorder, often called a fast ‘analog-to-digital converter’ or ‘ADC’, is typically employed to record the detector output amplitude as a function of time to produce the ion ToF m/z spectrum.
A variety of different types and configurations of detectors are able to satisfy these requirements to varying degrees. These include magnetic electron multipliers; discrete dynode electron multipliers; microchannel plate electron multipliers; and microchannel plate electron multipliers in combination with electron-to-photon converters, such as phosphors and scintillators, coupled to a light detector, such as a photomultiplier tube, charge-coupled device, etc. Generally, detectors of all types are limited by practical considerations in the maximum absolute amplitude of output signal that can be produced. Furthermore, over some range of signal amplitudes lower than this absolute maximum output signal, the response of the detector is typically non-linear; that is, the gain of the detector varies with signal amplitude, the gain generally declining as the signal amplitude increases. For signal amplitudes lower than this non-linear region, the gain of the detector can be relatively constant, and this range in signal amplitudes is referred to as the ‘linear dynamic range’ of the detector. The linear dynamic range of a detector depends on the gain; generally, as the gain of a detector is increased, the linear dynamic range decreases. Consequently, the gain of a detector is typically limited in practice to a value that is low enough to ensure that the maximum intensity in a measured ToF spectrum does not exceed the upper limit of the linear dynamic range of the detector, so that the measured spectrum accurately reflect the relative abundances of the different m/z ions in the spectrum. However, this gain is often insufficient to produce a measurable output signal from single ions or from some few ions arriving at the detector simultaneously. In order to detect such low numbers of ions arriving simultaneously, including the case of the arrival of a single ion of any particular m/z value, the gain must frequently be greater than that which prevents the maximum signal amplitude in the spectrum from exceeding the linear dynamic range of the detector. A further consideration in determining the gain that is necessary to detect the arrival of single ions is that detectors generally produce an output signal for each ion arrival, or ‘hit’, that can vary substantially in amplitude from hit to hit. This variation in single-ion output pulse amplitude for a detector is described by its so-called ‘pulse height distribution’ characteristic. The gain needs to be adjusted to a level that is high enough to ensure that as many of the single ion hits will be detected and recorded as possible. However, when detectors are operated in this condition, the largest ion intensities in a mass spectrum may produce a non-linear detector response, or even saturate the detector; that is, the incoming ion flux may become greater than that which produces the maximum possible output signal. Hence, the situation often arises in which the intensities of ions of different m/z values in a ToF mass spectrum may vary over a range that cannot be accommodated with a linear response by any detector of the prior art with any particular gain setting.
ToF m/z spectra are often measured by integrating a number of individual spectra in order to improve the overall dynamic range and signal-to-noise. For example, 100 individual spectra may be recorded at a rate of 10,000 spectra per second, and may be integrated to extend the signal dynamic range, in principle, by a factor of about 100, while also reducing any random noise in the spectrum by a factor of 10. The total time required for such a measurement would be 10 milliseconds, corresponding to a spectral acquisition rate of 100 integrated spectra per second. Nevertheless, as discussed above, the total signal dynamic range that may be achieved may be limited, in part, by the detector response characteristics when operated at a fixed gain. One approach that might, in principle, partly overcome this constraint would be to vary the gain of the detector between measurements of individual spectra. The total integrated spectrum might then exhibit greater dynamic range than if all the individual spectra were measured with a fixed gain. Unfortunately, it is usually impractical or undesirable in practice to rapidly adjust the gain of the detector from the acquisition of one spectrum to the next, because it is generally necessary to allow some time, typically on the order of milliseconds or longer, for the detector response to stabilize after the gain is changed. This delay would result in a severe reduction of the speed with which ToF spectra may be recorded, leading to a loss of sensitivity within a fixed acquisition time. Further, spectral acquisition speed is important in itself in many time-dependent analyses, such as when a mass spectrometer is used as a detector for a gas or liquid chromatographic separation, and a reduction in spectral acquisition speed would restrict the resolving power of the chromatographic separation.
When a fast ADC is used to record the output signal from the detector, the range of signal amplitudes that can be measured may also be restricted by the dynamic range characteristics of the ADC electronics. Currently available fast ADCs typically have a digitization range of 8 bits, corresponding to a full range of possible digital output values of from 0 to 255 counts. For the recording of single ion hits, it is typically necessary to adjust the gain of the detector, or that of an amplifier between the detector and the ADC input, so that single ion pulse amplitudes produce a signal at the ADC input that corresponds to several digitizer bits, on average. This is necessary in order to ensure that most of the single ion pulse amplitudes, which vary over some ‘pulse height distribution’, are large enough to register at least 1 bit count in the ADC conversion process. Otherwise, a significant number of single ions that produce detector output pulses with amplitudes that fall within the lower-amplitude region of the pulse height distribution, will not be recorded, resulting in substantial error in the intensities of small m/z peaks relative to that of large m/z peaks in a spectrum. However, with such a gain, the more intense peaks at other m/z values in a spectrum will often be large enough to overflow the ADC, that is, to produce a signal amplitude at the ADC input that corresponds to a digital ADC output value that is greater than 255 counts. Such saturation of the ADC may occur even for signal amplitudes that are still within the linear dynamic range of the detector itself. In this case, it is necessary to reduce the gain of the detector or signal amplifier so that the amplitude of the largest peak in the spectrum corresponds to an ADC output value less than 255 counts. Then, however, a significant number of single ion hits may not produce a signal amplitude at the ADC input that is large enough to register 1 bit count in the ADC output, resulting in substantial inaccuracies in the relative intensities of less intense m/z peaks in the measured spectrum. Hence, a compromise is often necessary when a fast ADC is used to measure ToF m/z spectra, as to whether to record ToF m/z spectra with a detector and/or amplifier gain that produces accurate relative abundances of ions with lower intensities in a spectrum, or with a detector and/or amplifier gain that produces accurate relative abundances of ions with higher intensities in a spectrum.
In an attempt to overcome the dynamic range limitations of an 8-bit ADC, Beavis reports in the J. Am. Soc. Mass Spectrom. 7,107 (1995) an arrangement consisting of two 8-bit ADC's that simultaneously record the signal from a ToF mass spectrometer. The ToF signal is coupled to each ADC by a separate amplifier, so that the gains of the amplifiers may be different. The gain of one amplifier is set low enough so that the largest signals in the spectra do not extent beyond the 255 count limit of the first ADC, while the gain of the other amplifier is adjusted high enough to ensure that low signals, which may not have been recorded by the first ADC due to their low amplitude, are recorded by the second ADC. By combining the spectra measured with the two ADC's properly on a pulse-by-pulse basis, the dynamic range was improved by a factor of 16 relative to that of a single 8-bit ADC, corresponding in an effective amplitude resolution of 12 bits. However, the signal dynamic range is nevertheless constrained by that of the multiplier, as discussed previously, which may only be alleviated by incorporating a multiple detector arrangement, in which the multiple detectors may have different multiplier gains.
Instead of recording the signal output amplitude as a function of time with a fast analog recorder, an alternative method of recording ToF m/z spectra is often employed which essentially entails the logical detection of the arrival of ions, and recording their arrival times, with a so-called ‘time-to-digital recorder’, or ‘TDC’. In this detection approach, the TDC only records the arrival of an ion or ions by detecting the occurrence of an output pulse from the detector at each increment in time, without regard for the amplitude of the output pulse. Typically, many TDC arrival time spectra are registered and added together to produce a histogram of the number of ions arriving as a function of flight time, which then represents the measured integrated ToF m/z spectrum. Because the amplitude of the detector output signal is not recorded in such a scheme, the detector is typically operated with the highest practical gain, resulting in greater and more uniform single-ion pulse output amplitudes than when the detector is operated in the linear ‘analog’ mode, as described above with a fast ADC. Consequently, a so-called ‘discriminator’, which only allows the detection of pulses with amplitudes above some threshold, can be employed to distinguish pulses due to ions from noise pulses. Such discrimination can result in better signal-to-noise characteristics than is typical with the fast ADC method of signal measurement. Also, with this TDC ‘pulse counting’ approach, the signal dynamic range depends only on the number of spectra that is practical to integrate into a single histogram spectrum, independent of the limited dynamic range characteristics of the detector itself. Therefore, this approach can result in a greater linear dynamic range than would be allowed by either the detector response characteristics when operated as a linear analog amplifier, and/or the limited bit resolution of an ADC, provided that a sufficient number of spectra are integrated.
The TDC approach offers other advantages over the fast ADC approach. Generally, TDC pulse counting electronics, which need not be burdened by an analog digitization process, can exhibit substantially better time resolution than fast ADCs. The use of a TDC can therefore result in substantially better m/z ToF resolving power than with a fast ADC, provided that other limitations to the m/z resolving power are not dominant. Another advantage of a TDC is that the amount of data produced for each spectrum is dramatically less than the data produced when an ADC is utilized. The reason for this is that a TDC produces a data value only when a detector output pulse is detected, which is typically very infrequent relative to the total number of time steps or ‘bins’ comprising a TDC spectrum. In contrast, a fast ADC produces a data value at every time increment over the entire duration of a spectrum measurement. Therefore, TDC data presents much less of a burden to the data processing system than that from a fast ADC.
On the other hand, the TDC approach is severely restricted in dynamic range within individual spectra, because a TDC is unable to distinguish between the arrival of a single ion and the simultaneous arrival of more than one ion. Also, TDC's typically exhibit a ‘dead time’ following the recording of a pulse, during which time the TDC is unable to register the arrival of any additional ions. Therefore, the use of a TDC to record m/z spectra is limited to situations in which the ion flux is low enough to ensure that the probability of arrival of more than one ion within the dead time of the TDC is less than about 0.1 for the most intense peaks in a m/z spectrum. This is necessary to ensure that very few ions are missed because they arrived too close together in time. Hence, the use of a TDC for accurate measurement of relative ion abundances is limited to analytical situations in which the ion flux is relatively low, and in which sufficient time is available to integrate enough individual spectra to achieve acceptable signal dynamic range.
A number of schemes have been developed to improve the linear dynamic range of mass spectrometer detection systems. For example, Yoichi, in U.S. Pat. No. 4,691,160, describes a discrete dynode multiplier with two collector electrodes, which are of different areas, at the output of the multiplier. Each detector may be connected to separate amplifier electronics, and one set of signal recording electronics may be connected to either of the two amplifier outputs via a switch. Each collector produces an output signal amplitude in proportion to its collection area. Also, the two separate amplifiers may operate with different gains. Therefore, depending on the amplitude of the signal, one collector/amplifier combination or the other may be selected so as to maintain the signal amplitude within the signal dynamic range of the recording electronics. This approach still limits, however, the signal dynamic range that may be accommodated within a m/z spectrum to the inherently limited linear dynamic range of the multiplier.
Kristo and Enke, in Rev. Sci. Instrum. 59 (3), 438-442 (1988), described a detector configuration for a scanning mass spectrometer that consisted basically of two channel type electron multipliers in series. An intermediate anode collector was located so as to intercept 90% of the output current from the first multiplier; the rest of the output current from the first multiplier then entered the second multiplier and was further amplified. An analog amplifier was connected to the collector of the first multiplier, and a pulse counter was connected to the collector of the second multiplier. The signal output from each of the multipliers was electronically combined to produce a composite spectrum, wherein the signal from the first multiplier was selected for intensities corresponding to more than a single ion, and the signal from the second multiplier was selected for intensities corresponding to single ions. The dynamic range that was achieved was greater than a conventional detector that employed either of these modes.
Buckley, et. al., in U.S. Pat. No. 5,463,219, described an improved method of utilizing a so-called ‘simultaneous mode’ electron multiplier detector in a scanning mass spectrometer. Similar to the multiple-multiplier detector structure described by Kristo and Enke, the multiplier described by Buckley, et. al., incorporates a collector electrode which is located so as to intercept a portion of the amplified current at an intermediate stage of multiplication in the multiplier structure. The remainder of the current continues the process of amplification along the rest of the multiplier structure to the final output where the current is intercepted at the final collector. The first intermediate collector was connected to an analog signal processing electronics, while the output from the final stage collector was connected to pulse counting electronics. In contrast to Kristo and Enke, however, the approach of Buckley, et. al., was to record the signals from the analog and digital outputs simultaneously. The spectra recorded by both types of recording methods were then available for processing and cross calibration after the spectra were acquired, which allowed better accuracy of peak intensities than if the choice between signal recording methods was made ‘on the fly’ during spectra recording.
The discrete dynode and channel electron multiplier (CEM) structures of the above prior art allow access to an intermediate stage of multiplication, at which point an intermediate collector electrode may be located in a relatively straightforward manner. However, these types of structures do not typically produce output signals with as fast a response time as that from a so-called ‘channel-plate’ electron multiplier (CPEM). A CPEM achieves electron multiplication over a much shorter path length, resulting in much less transit time broadening of the signal, than with the other types of detectors, which require much longer lengths for the multiplication process. Therefore, a CPEM generally results in better m/z resolving power when used as a ToF mass spectrometer detector than other types of detectors. However, because of its compact structure, it is not possible or practical to incorporate an intermediate collector electrode at an intermediate stage of multiplication. However, Soviet Inventors Certificate SU 851549 teaches the disposition of a control grid between two CPEMs. By adjusting the potential on the control grid, the overall gain of the detector assembly output can be controlled. Also, U.S. Pat. No. 5,689,152 teaches a similar control grid disposed between certain dynode sheets in an electron multiplier composing a stack of such sheets.
There have also been attempts to improve the detection capability of the TDC approach for recording simultaneously arriving ions in a ToF mass spectrometer. Rockwood and Davis describe, in U.S. Pat. No. 5,777,326, a detector configuration comprising a microchannel plate multiplier and an array of collector anodes disposed to receive the microchannel plate output current, where each collector anode receives the output current from a different area of the microchannel plate, and each collector anode is coupled to an independent discriminator and TDC counting electronics. This arrangement allows multiple ions arriving simultaneously to all be counted without loss, provided that the probability is low that more than one ion produces a signal at any one anode within the dead time of the detector and counting electronics. This approach obviously becomes very cumbersome and expensive to implement due to the multiplicity of parallel TDC counting electronics that are required. Also, the dynamic range that can be achieved in practice is constrained by the number of anodes, and by the requirement that the ion flux must be low enough to allow single ion counting with any one anode.
A somewhat different approach was described by Bateman, et. al., in U.S. Pat. No. 6,229,142 B1, which also comprised a ToF TDC-based detector consisting of a microchannel plate multiplier with multiple anodes. However, instead of a multiplicity of uniformly sized anodes, Bateman, et. al. describe a detector with multiple anodes that are of substantially different areas, each of which is connected to separate TDC electronics. Because of the difference in collection efficiency for anodes of different areas, the signal from one anode or another may be selected according to the anode that produces the most valid results, depending on the signal intensity. The dynamic range that may be realized with this configuration is improved over that of a single anode with a TDC, but, obviously, the dynamic range of this approach is nevertheless constrained by the fact that no more than one ion may be counted for each anode, as with the multi-anode configuration of Rockwood and Davis.